Formaldehyde → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-hydroxy-2-butynyl)piperazine

HRID 584208Notes

Reaction equation

HRID 584208 reaction equation
C=O.[F:3][C:4]([F:33])([F:32])[C:5]1[CH:6]=[C:7]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[C:8]([N:10]1[CH2:15][CH2:14][NH:13][CH2:12][C@H:11]1[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([CH3:24])[CH:18]=1)=[O:9].[CH2:34]([OH:37])[C:35]#[CH:36].[I-].[K+].[C:40](=O)([O-])O.[Na+]>O1CCOCC1.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[F:33][C:4]([F:3])([F:32])[C:5]1[CH:6]=[C:7]([CH:25]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:27]=1)[C:8]([N:10]1[CH2:15][CH2:14][N:13]([CH2:40][C:36]#[C:35][CH2:34][OH:37])[CH2:12][C@H:11]1[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([CH3:24])[CH:18]=1)=[O:9]

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 4875Potassium IodideHCID 7859Propargyl alcoholHCID 516892Sodium BicarbonateHCID 54478438(2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine

Product 1

HCID 86588520(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-hydroxy-2-butynyl)piperazine

Reagents, catalysts & solvents 2

HCID 24463Copper sulfate pentahydrateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 37% aqueous formaldehyde (0.21 g), (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine (0.75.g), propargyl alcohol (0.11 ml), copper(II) sulfate pentahydrate (1.3 mg) and potassium iodide (2.8 mg) in 1,4-dioxane was stirred at 100° C. for 2 hours. After being cooled to room temperature, the mixture was made basic with aqueous saturated sodium hydrogen carbonate solution. The resulting mixture was filtered and the filtrate was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixed solvent of n-hexane and ethyl acetate (4:1). The fractions containing the objective compound was collected and evaporated under reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-hydroxy-2-butynyl)piperazine (0.78 g) as a syrup.

Workup

  1. temperatureAfter being cooled to room temperature
  2. filtrationThe resulting mixture was filtered
  3. extractionthe filtrate was extracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel using a mixed solvent of n-hexane and ethyl acetate (4:1)
  8. additionThe fractions containing the objective compound
  9. customwas collected
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-53559e9e13004f18822b7469771586da
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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